逍遥散防治雷公藤多苷致肝损伤的作用机制  

Mechanism of Xiaoyaosan in Preventing and Treating Hepatic Injury Caused by Tripterygium Glycosides

作　　者：李媛媛[1] 王一旭 王浩[1] 张碧涛 王少贤[1,2] 李振彬 LI Yuan-yuan;WANG Yi-xu;WANG Hao;ZHANG Bi-tao;WANG Shao-xian;LI Zhen-bin(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Integrated Traditional Chinese and Western Medicine,Bethune International Peace Hospital,People's Liberation Army,Shijiazhuang 050000,China)

机构地区：[1]河北中医学院,石家庄050200 [2]中国人民解放军白求恩国际和平医院,石家庄050000

出　　处：《中国实验方剂学杂志》2020年第23期76-82,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81873301);河北中医学院2020年研究生创新资助立项项目(XCXZZSS2020017)。

摘　　要：目的:观察逍遥散对雷公藤多苷连续灌胃5周所致大鼠肝损伤的防治作用。方法:将31只SD大鼠随机分为4组,分别为正常组、雷公藤多苷组、雷公藤多苷+逍遥散组(治疗组)、雷公藤多苷+逍遥散提前用药1周组(防治组)。雷公藤多苷按37.5 mg·kg-1灌胃给药,逍遥散(水煎剂)按19.270 g·kg-1灌胃给药。首先防治组每天上午8:00~9:00灌胃逍遥散,其他组灌胃等体积生理盐水。1周后,雷公藤多苷组每天上午8:00~9:00灌胃雷公藤多苷混悬液;治疗组和防治组每天上午8:00~9:00灌胃逍遥散,2 h后再灌胃雷公藤多苷混悬液,给药持续5周。采用苏木素-伊红(HE)染色法观察肝组织病理形态学改变,酶联免疫吸附测定(ELISA)检测各组大鼠血清白细胞介素-1β(IL-1β),白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α)水平,化学法检测天门冬氨酸氨基转移酶(AST),丙氨酸氨基转移酶(ALT),谷胱甘肽过氧化物酶(GSH-Px),超氧化物歧化酶(SOD),微量丙二醛(MDA)水平变化,免疫组织化学染色观测肝组织IL-6,IL-1β,TNF-α阳性表达情况。结果:与正常组比较,雷公藤多苷组炎细胞浸润,肝细胞水肿,肝血窦受挤压变窄,肝板变宽,肝细胞出现明显坏死,血清IL-1β,IL-6,TNF-α,ALT,AST,MDA水平显著升高(P<0.01),GSH-Px,SOD水平明显下降(P<0.05,P<0.01),肝组织IL-6,TNF-α,IL-1β阳性表达显著增强(P<0.01);与雷公藤多苷组比较,治疗组与防治组大鼠肝组织少部分炎细胞浸润,水肿减轻,部分细胞紊乱,血清IL-1β,IL-6,TNF-α,ALT,AST,MDA水平显著下降(P<0.01),GSH-Px,SOD水平明显升高(P<0.05),肝组织IL-6,TNF-α,IL-1β阳性表达均显著减少(P<0.01),且防治组疗效更好。结论:逍遥散在一定程度上能明显缓解雷公藤多苷所致长期肝毒性,且提前预防性给药效果较佳。Objective:To observe the preventive and therapeutic effects of 5-week administration with Xiaoyaosan on rat liver injury caused by tripterygium Glycosides. Method: Thirty-one SD rats were randomly divided into 4 groups, namely normal group, tripterygium glycosides group, tripterygium glycosides+Xiaoyaosan group(treatment group),and tripterygium glycosides+Xiaoyaosan for 1 week in advance group(prevention group). Tripterygium glycosides(37.5 mg·kg-1)was administered intragastrically,and Xiaoyaosan(water decoction,19.270 g·kg-1)was administered intrastrically. First,the rats of prevention group were intragastrically administrated with Xiaoyaosan at 8:00-9:00 am,and the rats of other groups were given an equal volume of normal saline. After 1 week,the rats of tripterygium glycosides group were administered intragastrically with tripterygium glycosides suspension at 8:00-9:00 am. The rats of the treatment group and the prevention group were intragastrically administrated with Xiaoyaosan at 8:00-9:00 am,and then tripterygium glycosides suspension 2 hours later. All the drugs were given once a day for 5 weeks. Hematoxylin-eosin(HE)staining was used to observe the pathological changes of liver,enzyme-linked immunosorbent assay(ELISA)was used to detect serum interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),chemical method was used to detect the content changes of aspartate aminotransferase(AST), alanine aminotransferase(ALT), glutathione peroxidase(GSH-Px), superoxide dismu-tase(SOD), trace malondiamine aldehyde(MDA). Immunohist-ochemical staining was used to observe the expressions of IL-6,IL-1β and TNF-α in liver tissue. Result: Compared with the normal group,the tripterygium glycosides group showed inflammatory cell infiltration,hepatocyte edema,hepatic sinuses squeezing and narrowing,liver plate widening,and liver cell necrosis,the contents of serum IL-1β,IL-6,TNF-α,ALT,AST and MDA were significantly increased(P<0.01),but the contents of GSH-Px and SOD were decreased significantly

关 键 词：逍遥散 雷公藤多苷 肝损伤 肝功能 氧化损伤 炎症因子 

分 类 号：R2-0[医药卫生—中医学] R22